Core Insights - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][3] - The CEO, Faraz Ali, will participate in a fireside chat at the Morgan Stanley 23rd Annual Global Healthcare Conference on September 9, 2025 [1] - The company has a pipeline that includes clinical-stage candidates TN-201 and TN-401, targeting specific genetic heart conditions [3] Company Overview - Tenaya Therapeutics aims to address the underlying causes of heart disease through innovative therapies [3] - The company utilizes integrated capabilities such as target validation and capsid engineering to develop its drug portfolio [3] - Current clinical-stage products include TN-301, a small molecule HDAC6 inhibitor for heart failure, along with several early-stage programs [3]

Core Insights - Tenaya Therapeutics presented interim data from the MyClimb study, the largest noninterventional natural history study of pediatric patients with MYBPC3-associated hypertrophic cardiomyopathy (HCM), at the European Society of Cardiology Congress [1][2][5] Group 1: Study Overview - MyClimb study includes over 200 participants diagnosed with MYBPC3-associated HCM before age 18, with data collected from 27 centers across the U.S., Canada, Spain, and the UK [2][5] - The study aims to characterize the relationship between genotype and cardiac measures over time, initiated in 2021 [5] Group 2: Key Findings - 93% of participants had the nonobstructive form of HCM, which currently lacks approved treatment options [3] - Genetic inheritance patterns revealed distinct risk profiles among participants, with nearly all Homozygous group members dying or requiring heart transplants before age one [3] - Compound Heterozygous participants had a median diagnosis age of 2.9 years, with 63% experiencing heart failure-related hospitalizations [3] - Heterozygous children had a median diagnosis age of 6.5 years, with 27% facing heart failure-related hospitalizations [3] Group 3: Predictive Risk Factors - Left Ventricular Mass Index (LVMI) was identified as a significant predictor of risk, with every 10-unit increase associated with a 10% higher hazard of serious events [3] - Genetic profiles and LVMI may inform risk stratification and intervention strategies for pediatric patients [2][3] Group 4: Gene Therapy Development - TN-201 is a gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells, with initial data from the first three patients presented at a prior meeting [7] - The therapy has received Fast Track, Orphan Drug, and Rare Pediatric Drug Designations from the FDA, indicating its potential significance in treating this condition [7] Group 5: Company Background - Tenaya Therapeutics focuses on developing curative therapies for heart disease, with a pipeline that includes TN-201 for MYBPC3-associated HCM and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [8]

Summary of Tenaya Therapeutics (TNYA) KOL Webcast Event Company Overview - **Company**: Tenaya Therapeutics (TNYA) - **Focus**: Development of curative therapies for genetic cardiomyopathies, specifically through gene therapy approaches targeting underlying causes of heart disease [6][7][8] Key Points Discussed Industry Context - **Gene Therapy for Cardiomyopathies**: Tenaya is positioned as an emerging leader in gene therapy for inherited heart conditions, with a focus on addressing root causes rather than symptoms [6][7] - **Pipeline**: The company has three clinical-stage programs, including two novel gene therapies with near-term data readouts [6][7] Clinical Programs 1. **TN-201**: - Target: Hypertrophic Cardiomyopathy (HCM) due to MyBPC3 gene mutations - Status: Advancing towards pivotal studies with data readout planned for Q4 2025 [7][8][21] - Initial data showed positive tolerability and improvements in cardiac hypertrophy measures [21][22] 2. **TN-401**: - Target: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by PKP2 gene mutations - Status: Ongoing RIDGE-1 clinical study with initial data readout also planned for Q4 2025 [8][23][29] - Focus on safety and efficacy in reducing arrhythmic events and halting heart failure progression [29] Scientific Methodology - **Protein Measurement**: The company emphasizes the importance of measuring protein expression as a surrogate marker for gene therapy efficacy [10][12][35] - **Biopsy Analysis**: Cardiac biopsies are collected to assess gene therapy success through DNA, RNA, and protein quantification [31][32][35] - **Mass Spectrometry**: Utilized for precise protein quantification, allowing for a detailed view of protein levels in complex tissues like the heart [51][52][80] Challenges and Innovations - **Haploinsufficiency**: The majority of patients have one working gene, complicating the measurement of therapeutic protein levels [10][36] - **Normalization Strategies**: The importance of proper normalization techniques in protein measurement to ensure accurate results [56][63] - **Collaboration with Experts**: Engaging with leading experts in the field to refine methodologies and validate findings [37][38][79] Future Expectations - **Data Readouts**: Anticipated data readouts for both TN-201 and TN-401 in Q4 2025, which will provide insights into the efficacy and safety of the therapies [21][22][29] - **Longitudinal Studies**: Ongoing analysis of patient samples to track changes over time, enhancing the understanding of treatment effects [86] Additional Insights - **Patient-Centric Approach**: The company maintains a strong focus on patient outcomes and quality of life improvements through innovative therapies [6][7] - **Regulatory Considerations**: The potential for accelerated approvals based on protein expression as a surrogate marker for efficacy, supported by recent FDA precedents [10][12] This summary encapsulates the critical aspects of Tenaya Therapeutics' KOL webcast, highlighting the company's innovative approach to gene therapy for cardiomyopathies, the status of its clinical programs, and the methodologies employed to measure therapeutic efficacy.

Pipeline and Programs - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease[9] - TN-201, a gene therapy for MYBPC3-associated HCM, is in Phase 1b/2 clinical trials with data readouts expected in Q4 2025[10, 12] - TN-401, a gene therapy for PKP2-associated ARVC, is in Phase 1b clinical trials with initial data including safety and biopsy results expected in 2025[10, 94] - TN-301, a small molecule HDAC6 inhibitor for HFpEF, has completed Phase 1 trials and is seeking a partner for further development[10, 99, 104] TN-201 for MYBPC3-associated HCM - MYBPC3-associated HCM affects an estimated 120,000 people in the U S alone[22] - Interim Cohort 1 data for TN-201 showed the therapy was well-tolerated at 3E13 vg/kg dose, with no cardiotoxicities and manageable liver enzyme elevations[17, 40] - All three patients in Cohort 1 improved from NYHA class II/III to NYHA class I, and elevated troponin levels dropped by 60% in two patients into normal ranges[19] - TN-201 DNA in cardiac biopsy surpassed preclinical efficacy threshold and compares favorably to peer, with long-term stability achieved[42] - TN-201 RNA expression increased by as much as 13-fold from week 8 to Week 52[46] TN-401 for PKP2-associated ARVC - PKP2-associated ARVC is estimated to affect over 70,000 people in the U S [75] - Preclinical studies showed that a single 3E13 vg/kg dose of TN-401 in a KO mouse model reversed hallmarks of the disease and extended survival[91] - RIDGE natural history study shows that over 80% of ARVC patients continue to experience high PVC count despite standard of care treatments[87]

Summary of Tenaya Therapeutics (TNYA) FY Conference Call Company Overview - **Company**: Tenaya Therapeutics (TNYA) - **Founded**: 2016 - **Mission**: Focus on therapies for heart disease, including both rare genetic forms and prevalent forms [3][4] Pipeline and Clinical Development - **Clinical Stage Assets**: Three clinical stage assets currently in development [4] - **Gene Therapies**: Focus on gene therapies for genetic causes of cardiomyopathy and a small molecule for HFpEF [4] - **Clinical Sites**: Over 40 clinical sites active in seven countries for patient recruitment [4] Gene Therapy Programs TN-201 for MYBPC3 Positive Hypertrophic Cardiomyopathy - **Target Disease**: Leading genetic cause of hypertrophic cardiomyopathy, affecting approximately 120,000 patients in the US [15] - **Mechanism**: Addresses deficiency of myBPC3 protein, leading to heart thickening and potential heart failure [16][17] - **Natural History Study**: MyCLIMB study with over 220 children enrolled to characterize disease progression [20][21] - **Phase 1b Study**: Completed dosing of high dose cohort; initial results show improvement in heart function [25][27] - **Upcoming Data**: Full cohort data expected in Q4 2025, with focus on safety and efficacy [37] TN-401 for PKP2-Related Arrhythmogenic Right Ventricular Cardiomyopathy - **Target Disease**: Accounts for about 40% of arrhythmogenic right ventricular cardiomyopathy cases, approximately 70,000 patients in the US [44] - **Mechanism**: Aims to add a copy of the human gene to improve desmosome function and reduce arrhythmia burden [46] - **Biopsy Data**: Expected in Q4 2025, focusing on vector copy number, RNA, and protein levels [50][51] Safety and Efficacy - **AAV9 Vector**: Selected for its extensive safety database and effectiveness in cardiac applications [5][6] - **Safety Record**: No significant safety issues reported in ongoing trials; adverse events consistent with other gene therapies [13][14] - **Patient Outcomes**: Initial data shows symptomatic improvement in patients treated with TN-201 [25][27] Small Molecule Program TN-301 - **Status**: Completed first-in-human study with 72 patients; well tolerated with no dose-limiting toxicities [55] - **Future Plans**: Exploring opportunities to advance the program, focusing on HFpEF and potentially severe rare diseases [56] Key Takeaways - **Market Opportunity**: Both TN-201 and TN-401 target large orphan conditions with significant unmet medical needs [44][46] - **Data Releases**: Important data updates expected in Q4 2025 for both gene therapy programs, which could influence future clinical development strategies [37][50]

Clinical Programs & Data - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease [9] - TN-201 for MYBPC3-associated HCM plans data release including longer-term follow-up for Cohort 1 (3E13 vg/kg) and initial safety and biopsy results for Cohort 2 (6E13 vg/kg) in Q4'25 [15] - TN-401 for PKP2-associated ARVC plans data release will include initial Cohort 1 (3E13 vg/kg) data focused on safety and biopsy results in Q4'25 [16] - Interim Cohort 1 TN-201 data showed improvements in ≥ 1 measures of hypertrophy in two of three patients [17] Disease & Patient Populations - MYBPC3-associated HCM is estimated to affect 120,000 people in the U S alone [22] - Approximately 57% of identified genetic variants underlying familial HCM are MYBPC3 mutations [22] - Over 30% of genetic variants underlying childhood-onset HCM are MYBPC3 mutations [22] - PKP2-associated ARVC is estimated to affect >70,000 people in the U S [75] - In ARVC patients, >15% of heart-related deaths in patients < 35 are due to ARVC [75] - In ARVC patients, 23% of ARVC patients present with sudden cardiac death [75] - In ARVC patients, 40% of ARVC patients carry pathogenic PKP2 mutations [75] Capabilities & Milestones - Tenaya has cGMP AAV manufacturing scale achieved; 1000L clinical supply for TN-201 and TN-401 ready [115]

Core Insights - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][3] - The company will participate in the Canaccord Genuity 45 Annual Growth Conference on August 12, 2025 [1] Company Overview - Tenaya's mission is to discover, develop, and deliver therapies that target the underlying causes of heart disease [3] - The company's pipeline includes clinical-stage candidates TN-201 for MYBPC3-associated hypertrophic cardiomyopathy and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [3] - Tenaya employs integrated capabilities such as target validation, capsid engineering, and manufacturing to create novel medicines based on genetic insights [3] - Additional products in development include TN-301, a small molecule HDAC6 inhibitor for heart failure, and various early-stage programs targeting rare genetic disorders and common heart conditions [3]

Core Viewpoint - Tenaya Therapeutics reported a narrower net loss in Q2 2025 compared to analyst expectations and the previous year, highlighting progress in clinical programs and cost management [1][2]. Financial Performance - The company posted a GAAP net loss per share of $(0.14) for Q2 2025, an improvement of 58.8% from $(0.34) in Q2 2024 [2]. - Total net loss for the quarter was $23.3 million, down 20.8% from $29.4 million in the same quarter last year [2][5]. - Research and Development expenses decreased by 23.0% to $17.4 million from $22.6 million in Q2 2024 [2]. - General and Administrative expenses fell to $6.7 million, down 18.3% from $8.2 million in Q2 2024 [2][5]. - The company ended the quarter with $71.7 million in cash and equivalents, an increase from $61.4 million at the end of 2024 [6]. Business Overview - Tenaya Therapeutics focuses on developing gene therapies for life-threatening heart diseases caused by genetic mutations, specifically targeting hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy [3]. - The company utilizes adeno-associated virus (AAV) vectors to deliver corrective DNA to affected heart cells [3]. Clinical Developments - TN-201 completed enrollment for its first two cohorts in the MyPEAK-1 Phase 1b/2 trial, with positive interim results showing improvement in heart function [7]. - TN-401 completed the first patient cohort in its RIDGE-1 Phase 1b trial and began dosing a second cohort at a higher gene vector dose, with early safety results leading to dose escalation approval [8]. - Both therapies have received FDA orphan drug and Fast Track designations, facilitating their development [10]. Strategic Focus - The company aims to advance its gene therapy programs while managing costs and enhancing its intellectual property and manufacturing capabilities [4]. - Tenaya is committed to independent pipeline progress and has not announced new business development or partnership deals [12]. Outlook - The company projects that its current cash reserves will support operations into the second half of 2026, providing a runway before needing additional financing [14].

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) Presents Tenaya Therapeutics' unaudited condensed financial statements for the three and six months ended June 30, 2025 Condensed Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $62,671 | $4,323 | | Total current assets | $75,875 | $67,375 | | Total assets | $122,151 | $119,940 | | **Liabilities & Equity** | | | | Total current liabilities | $12,654 | $15,975 | | Total liabilities | $22,323 | $27,086 | | Accumulated deficit | $(564,558) | $(514,411) | | Total stockholders' equity | $99,828 | $92,854 | Condensed Statements of Operations Highlights (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $17,370 | $22,649 | $38,446 | $47,704 | | General and administrative | $6,712 | $8,174 | $13,174 | $16,881 | | **Loss from operations** | **$(24,082)** | **$(30,823)** | **$(51,620)** | **$(64,585)** | | **Net loss** | **$(23,283)** | **$(29,431)** | **$(50,147)** | **$(61,659)** | | Net loss per share | $(0.14) | $(0.34) | $(0.37) | $(0.74) | Condensed Statements of Cash Flows Highlights (Six Months Ended June 30, in thousands) | Cash Flow Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(38,725) | $(52,277) | | Net cash provided by investing activities | $47,290 | $17,126 | | Net cash provided by financing activities | $49,783 | $47,341 | | **Net change in cash** | **$58,348** | **$12,190** | [Notes to Unaudited Condensed Financial Statements](index=10&type=section&id=Notes%20to%20Unaudited%20Condensed%20Financial%20Statements) Detailed notes provide context for financial statements, covering business, liquidity, accounting policies, financing, and material events - The company is a clinical-stage biotechnology firm focused on therapies for heart disease, with lead candidates TN-201, TN-401, and TN-301[27](index=27&type=chunk) - In March 2025, the company completed an underwritten offering of common stock and warrants, receiving net proceeds of approximately **$48.8 million**[29](index=29&type=chunk)[71](index=71&type=chunk) - Management believes that existing cash, investments, and available funds under its loan agreement are sufficient to fund operations for at least the next twelve months, supported by recent cost containment measures including a workforce reduction[31](index=31&type=chunk) - In January 2025, the company repriced approximately **4.1 million** employee stock options to an exercise price of **$1.21**, resulting in an incremental stock-based compensation expense of **$1.3 million**[55](index=55&type=chunk)[57](index=57&type=chunk) - A workforce reduction was initiated in March 2025, with expected aggregate charges of **$1.6 million to $2.7 million**, primarily for severance, with **$1.1 million** recognized in the first six months of 2025[84](index=84&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=21&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses business overview, clinical development of lead gene therapy candidates, financial results, liquidity, and capital resources [Overview](index=21&type=section&id=Overview) Tenaya, a clinical-stage biotech, focuses on developing heart disease therapies, with TN-201 and TN-401 gene therapies in Phase 1b/2 trials - The company's primary focus is on the clinical development of its lead gene therapy candidates, TN-201 (for HCM) and TN-401 (for ARVC)[95](index=95&type=chunk) - For the TN-201 MyPEAK-1 trial, enrollment in both dose cohorts is complete, with initial data from the higher-dose Cohort 2 expected in **Q4 2025**[97](index=97&type=chunk) - For the TN-401 RIDGE-1 trial, the first patient in the higher-dose Cohort 2 was dosed in July 2025, with initial clinical data from Cohort 1 expected in **Q4 2025**[103](index=103&type=chunk) [Results of Operations](index=24&type=section&id=Results%20of%20Operations) Details financial performance for Q2 and H1 2025, showing decreased operating expenses and a lower net loss due to workforce reductions Comparison of Operating Expenses (in thousands) | Expense Category | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $17,370 | $22,649 | $38,446 | $47,704 | | General and administrative | $6,712 | $8,174 | $13,174 | $16,881 | | **Total operating expenses** | **$24,082** | **$30,823** | **$51,620** | **$64,585** | - The decrease in R&D expenses for Q2 2025 was primarily driven by a **$2.6 million** reduction in manufacturing costs and a **$1.1 million** decrease in clinical trial costs, reflecting the impact of workforce reductions[124](index=124&type=chunk) - The decrease in R&D expenses for H1 2025 was primarily due to a **$3.7 million** reduction in manufacturing costs and a **$3.0 million** decrease in clinical trial costs[131](index=131&type=chunk) [Liquidity and Capital Resources](index=26&type=section&id=Liquidity%20and%20Capital%20Resources) As of June 30, 2025, Tenaya held $71.7 million in cash and investments, with management confirming sufficient funds for the next twelve months - As of June 30, 2025, the company had cash, cash equivalents, and investments in marketable securities of **$71.7 million** and an accumulated deficit of **$564.6 million**[129](index=129&type=chunk) - The company believes its existing cash and available funds from its Loan Agreement with SVB will be sufficient to meet working capital needs for at least the next twelve months[138](index=138&type=chunk) - Recent financing activities include a March 2025 follow-on offering (net proceeds of **~$48.8 million**) and sales under an "at-the-market" (ATM) offering in January 2025 (net proceeds of **$0.9 million**)[134](index=134&type=chunk)[136](index=136&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=30&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Tenaya is exempt from providing quantitative and qualitative disclosures about market risk - The company is a smaller reporting company and is not required to provide quantitative and qualitative disclosures about market risk[157](index=157&type=chunk) [Item 4. Controls and Procedures](index=30&type=section&id=Item%204.%20Controls%20and%20Procedures) Management confirmed effective disclosure controls and procedures as of June 30, 2025, with no material changes in internal control over financial reporting - Management concluded that as of the end of the period, the company's disclosure controls and procedures were effective[158](index=158&type=chunk) - There were no changes in internal control over financial reporting during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, internal controls[159](index=159&type=chunk) PART II—OTHER INFORMATION [Item 1. Legal Proceedings](index=31&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material litigation or legal proceedings that would adversely affect its business - The company is not currently involved in any material legal proceedings[162](index=162&type=chunk) [Item 1A. Risk Factors](index=31&type=section&id=Item%201A.%20Risk%20Factors) Outlines significant risks: early development, net losses, capital dependence, clinical trial uncertainties, manufacturing, regulatory, competition, IP, and delisting risk - The company has a limited operating history, no products approved for sale, and has incurred a significant accumulated deficit of **$564.6 million** as of June 30, 2025[166](index=166&type=chunk)[170](index=170&type=chunk) - The company requires substantial additional capital to finance operations and may be forced to delay or eliminate programs if funding is not available on acceptable terms[178](index=178&type=chunk) - The company received a notice from Nasdaq on April 15, 2025, for failing to meet the minimum bid price requirement of **$1.00** per share, and its common stock could be delisted if compliance is not regained[403](index=403&type=chunk)[405](index=405&type=chunk) - The company faces potential patent infringement claims related to its TN-201 product candidate and the use of AAV vectors, which could result in liability for damages or require obtaining a license[340](index=340&type=chunk)[341](index=341&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=85&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No previously undisclosed unregistered equity security sales occurred during the reporting period - There were no sales of unregistered equity securities during the reporting period that were not previously reported[426](index=426&type=chunk) [Item 3. Defaults Upon Senior Securities](index=85&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is not applicable to the company [Item 4. Mine Safety Disclosures](index=85&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company [Item 5. Other Information](index=86&type=section&id=Item%205.%20Other%20Information) No director or officer adopted or terminated a Rule 10b5-1 or non-Rule 10b5-1 trading arrangement during the quarter - No director or officer adopted or terminated a Rule 10b5-1 trading arrangement during the quarter[432](index=432&type=chunk) [Item 6. Exhibits](index=87&type=section&id=Item%206.%20Exhibits) Lists exhibits filed with Form 10-Q, including certifications by executive officers and XBRL data files

[Executive Summary & Company Overview](index=1&type=section&id=Executive%20Summary%20%26%20Company%20Overview) Tenaya Therapeutics announced Q2 2025 results, detailing clinical progress for gene therapies TN-201 and TN-401, and maintaining a cash runway into the second half of 2026 [Introduction and Key Highlights](index=1&type=section&id=Introduction%20and%20Key%20Highlights) Tenaya Therapeutics announced its Q2 2025 financial results and provided a business update, highlighting significant progress in its gene therapy clinical trials for MYBPC3-associated HCM (TN-201) and PKP2-associated ARVC (TN-401), with positive DSMB reviews enabling dose escalation and expansion; the company anticipates key data readouts for both programs in Q4 2025 and maintains a cash runway into the second half of 2026 - **Enrollment completed** in Cohorts 1 and 2 of MyPEAK™-1 Phase 1b/2 trial for TN-201 (MYBPC3-associated HCM); positive DSMB safety review enables enrollment of expansion cohorts[1](index=1&type=chunk)[4](index=4&type=chunk) - Cohort 1 of RIDGE™-1 Phase 1b trial for TN-401 (PKP2-associated ARVC) **enrolled**, and first patient dosed in Cohort 2 following DSMB recommendation for dose escalation and expansion[1](index=1&type=chunk)[4](index=4&type=chunk) - Data readouts from both TN-201 and TN-401 clinical programs are planned for the **fourth quarter of 2025**[1](index=1&type=chunk)[4](index=4&type=chunk) - Tenaya Therapeutics has a **cash runway into the second half of 2026**[2](index=2&type=chunk)[14](index=14&type=chunk) [About Tenaya Therapeutics](index=3&type=section&id=About%20Tenaya%20Therapeutics) Tenaya Therapeutics is a clinical-stage biotechnology company dedicated to discovering, developing, and delivering curative therapies for heart disease, leveraging integrated internal capabilities for target validation, capsid engineering, and manufacturing - Tenaya Therapeutics is a clinical-stage biotechnology company focused on discovering, developing, and delivering potentially curative therapies for the **underlying causes of heart disease**[12](index=12&type=chunk) - The company's pipeline includes clinical-stage gene therapies **TN-201** (for MYBPC3-associated HCM) and **TN-401** (for PKP2-associated ARVC), a clinical-stage small molecule **TN-301** (HDAC6 inhibitor for heart failure), and multiple early-stage preclinical programs[12](index=12&type=chunk) [Business and Program Updates](index=1&type=section&id=Business%20and%20Program%20Updates) Tenaya Therapeutics provided updates on its clinical-stage gene therapy programs TN-201 and TN-401, highlighting trial progress, safety reviews, and upcoming data readouts, alongside advancements in research and manufacturing capabilities [TN-201 Gene Therapy for MYBPC3-Associated Hypertrophic Cardiomyopathy (HCM)](index=1&type=section&id=TN-201%20Gene%20Therapy%20for%20MYBPC3-Associated%20Hypertrophic%20Cardiomyopathy%20%28HCM%29) Tenaya Therapeutics has completed enrollment and dosing for Cohort 2 of the MyPEAK™-1 Phase 1b/2 trial for TN-201; a positive DSMB review confirmed an acceptable safety profile, allowing for dose expansion; interim data from Cohort 1 showed promising results, including robust transduction, increased RNA/protein expression, and clinical improvements in patients with severe disease - **Completed enrollment and dosing of three patients** at the 6E13 vg/kg dose level (Cohort 2) in the MyPEAK™-1 Phase 1b/2 clinical trial of TN-201 in May[5](index=5&type=chunk) - Independent DSMB determined TN-201 had an **acceptable safety profile**, enabling enrollment of dose expansion cohorts, with Tenaya anticipating enrolling patients in the 6E13 vg/kg dose expansion cohort[5](index=5&type=chunk) - Interim data from Cohort 1 (3E13 vg/kg) showed **robust transduction and RNA expression** with increasing RNA and protein levels over time; all three patients with severe disease at baseline achieved New York Heart Association Class I, and two experienced improvement in hypertrophy measures[6](index=6&type=chunk) - The MyClimb pediatric non-interventional natural history study has **enrolled over 200 patients at 29 sites worldwide** to characterize MYBPC3-associated HCM in patients under 18[9](index=9&type=chunk) [TN-401 Gene Therapy for PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)](index=2&type=section&id=TN-401%20Gene%20Therapy%20for%20PKP2-Associated%20Arrhythmogenic%20Right%20Ventricular%20Cardiomyopathy%20%28ARVC%29) Enrollment for Cohort 1 of the RIDGE™-1 Phase 1b trial for TN-401 was completed in April 2025; following a positive DSMB recommendation, enrollment for a higher dose Cohort 2 (6E13 vg/kg) has begun, with the first patient dosed; data from the RIDGE natural history study highlighted the high burden of arrhythmia and progressive structural changes in PKP2-associated ARVC patients, alongside low AAV9 immunity, suggesting broad eligibility for TN-401 - **Enrollment of the first cohort of three patients** receiving TN-401 at a dose level of 3E13 vg/kg in the RIDGE-1 Phase 1b clinical trial was completed in April 2025[9](index=9&type=chunk) - In July 2025, the RIDGE-1 DSMB issued a **positive recommendation for both enrollment of a higher dose cohort (6E13 vg/kg)** and additional patients at the 3E13 vg/kg dose; Cohort 2 enrollment is underway, and the first patient has been dosed at 6E13 vg/kg[9](index=9&type=chunk) - Data from the RIDGE natural history study (**191 participants**) indicated a **high burden of arrhythmia** (83% >500 PVCs/day, 49% history of VT) despite standard care, evidence of progressive structural changes, and low levels of preexisting immunity to AAV9 antibodies, making most participants eligible for TN-401[9](index=9&type=chunk) [Research and Manufacturing Capabilities](index=2&type=section&id=Research%20and%20Manufacturing%20Capabilities) Tenaya's Research and Manufacturing teams presented advancements in core capabilities at the American Society for Gene Therapy Annual Meeting, focusing on novel capsid engineering, genetic medicine design, and AAV gene therapy manufacturing - In May 2025, Tenaya's Research and Manufacturing teams presented posters at the **American Society for Gene Therapy 28th Annual Meeting**[8](index=8&type=chunk) - Presentations detailed efforts to advance core capabilities in **novel capsid engineering**, identification, design and optimization of cardiomyocyte-targeting genetic medicines, and manufacturing of AAV gene therapies[8](index=8&type=chunk) [Upcoming Events and Data Readouts](index=2&type=section&id=Upcoming%20Events%20and%20Data%20Readouts) Tenaya Therapeutics plans to release initial Cohort 2 data and an update on Cohort 1 for TN-401 in Q4 2025, along with meaningful new data for both TN-201 and TN-401; an abstract for the MyClimb study has been accepted for presentation at the ESC Annual Meeting, and the company will host a Virtual Key Opinion Leader event in August 2025 - Tenaya anticipates releasing initial Cohort 2 data and an update on Cohort 1 for TN-401 in the **fourth quarter of 2025**[9](index=9&type=chunk) - Meaningful new data readouts for both TN-201 and TN-401 clinical programs are planned for the **fourth quarter of 2025**[4](index=4&type=chunk) - An abstract regarding Tenaya's pediatric non-interventional natural history study, MyClimb, has been accepted for presentation at the upcoming **European Society of Cardiology (ESC) Annual Meeting** (August 29-September 1)[9](index=9&type=chunk) - Tenaya plans to host a Virtual Key Opinion Leader event, **'Measuring Protein Expression in Cardiac Gene Therapy,' on August 19, 2025**[14](index=14&type=chunk) [Financial Results](index=3&type=section&id=Financial%20Results) Tenaya Therapeutics reported a reduced net loss for Q2 2025 and H1 2025, driven by lower operating expenses, and maintained a cash position of $71.7 million, extending its runway into the second half of 2026 [Second Quarter 2025 Financial Highlights](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Highlights) Tenaya Therapeutics reported a net loss of $23.3 million for Q2 2025, an improvement from $29.4 million in Q2 2024, driven by reduced R&D and G&A expenses; the company ended the quarter with $71.7 million in cash, cash equivalents, and marketable securities, providing a cash runway into the second half of 2026 - Cash, cash equivalents and investments in marketable securities were **$71.7 million** as of June 30, 2025[14](index=14&type=chunk) - The company expects its current funds to support planned operations into the **second half of 2026**[14](index=14&type=chunk) Key Financial Highlights (Q2 2025 vs. Q2 2024) | Metric | Q2 2025 (in millions USD) | Q2 2024 (in millions USD) | Change (QoQ, millions USD) | | :----------------------- | :------------------------ | :------------------------ | :------------------------- | | Research & Development | $17.4 | $22.6 | -$5.2 | | General & Administrative | $6.7 | $8.2 | -$1.5 | | Net Loss | $(23.3) | $(29.4) | +$6.1 | | Net Loss Per Share | $(0.14) | $(0.34) | +$0.20 | [Condensed Statements of Operations](index=5&type=section&id=Condensed%20Statements%20of%20Operations) For the second quarter of 2025, Tenaya Therapeutics reported a net loss of $23.3 million, a decrease from $29.4 million in the prior year, primarily due to lower operating expenses; for the six months ended June 30, 2025, the net loss was $50.1 million, an improvement from $61.7 million in the same period of 2024 Condensed Statements of Operations (Three Months Ended June 30) | Metric | Q2 2025 (in thousands USD) | Q2 2024 (in thousands USD) | Change (QoQ, thousands USD) | | :----------------------- | :------------------------- | :------------------------- | :-------------------------- | | Research and development | $17,370 | $22,649 | -$5,279 | | General and administrative | $6,712 | $8,174 | -$1,462 | | Total operating expenses | $24,082 | $30,823 | -$6,741 | | Loss from operations | $(24,082) | $(30,823) | +$6,741 | | Interest income | $815 | $1,393 | -$578 | | Net loss | $(23,283) | $(29,431) | +$6,148 | | Net loss per share | $(0.14) | $(0.34) | +$0.20 | | Weighted-average shares | 162,791,579 | 85,706,501 | +77,085,078 | Condensed Statements of Operations (Six Months Ended June 30) | Metric | H1 2025 (in thousands USD) | H1 2024 (in thousands USD) | Change (YoY, thousands USD) | | :----------------------- | :------------------------- | :------------------------- | :-------------------------- | | Research and development | $38,446 | $47,704 | -$9,258 | | General and administrative | $13,174 | $16,881 | -$3,707 | | Total operating expenses | $51,620 | $64,585 | -$12,965 | | Loss from operations | $(51,620) | $(64,585) | +$12,965 | | Interest income | $1,449 | $2,845 | -$1,396 | | Net loss | $(50,147) | $(61,659) | +$11,512 | | Net loss per share | $(0.37) | $(0.74) | +$0.37 | | Weighted-average shares | 136,476,623 | 83,344,414 | +53,132,209 | [Condensed Balance Sheet Data](index=5&type=section&id=Condensed%20Balance%20Sheet%20Data) As of June 30, 2025, Tenaya Therapeutics reported an increase in cash, cash equivalents, and marketable securities to $71.7 million from $61.4 million at the end of 2024; total assets slightly increased, while total liabilities decreased over the same period Condensed Balance Sheet Data (As of June 30, 2025 vs. December 31, 2024) | Metric | June 30, 2025 (in thousands USD) | December 31, 2024 (in thousands USD) | Change (thousands USD) | | :--------------------------------- | :--------------------------------- | :--------------------------------- | :--------------------- | | Cash, cash equivalents and marketable securities | $71,667 | $61,446 | +$10,221 | | Total assets | $122,151 | $119,940 | +$2,211 | | Total liabilities | $22,323 | $27,086 | -$4,763 | | Total liabilities and stockholders' equity | $122,151 | $119,940 | +$2,211 | [Legal and Contact Information](index=3&type=section&id=Legal%20and%20Contact%20Information) This section provides standard disclaimers regarding forward-looking statements, outlining inherent risks and uncertainties, and lists key contact information for Tenaya Therapeutics [Forward-Looking Statements](index=3&type=section&id=Forward-Looking%20Statements) This section provides a standard disclaimer regarding forward-looking statements, emphasizing that they are based on current expectations and involve inherent risks and uncertainties; it outlines various factors that could cause actual results to differ materially from projections, including clinical trial outcomes, regulatory approvals, funding, and market conditions - The press release contains forward-looking statements based on current expectations, involving assumptions, risks, and uncertainties that may cause actual results to **differ**[13](index=13&type=chunk)[15](index=15&type=chunk) - Key risks include the timing and progress of clinical trials, unexpected safety events, potential failure of product candidates, differences from expected results, ability to obtain approvals, funding needs, reliance on third parties, competition, and **intellectual property protection**[15](index=15&type=chunk) - Tenaya assumes **no obligation to update or revise** any forward-looking statements, except as required by law[15](index=15&type=chunk) [Tenaya Contacts](index=4&type=section&id=Tenaya%20Contacts) This section provides contact information for Tenaya Therapeutics' corporate communications, investor relations, and media inquiries - Contact information is provided for **Michelle Corral** (VP, Corporate Communications and Investor Relations), **Anne-Marie Fields** (Precision AQ for Investors), and **Wendy Ryan** (Ten Bridge Communications for Media)[16](index=16&type=chunk)